The Plasmodium parasite is largely responsible for most of the infections, and therefore specific inhibitors of Plasmodium HKs (hexokinase) hold promise as therapeutic and transmission blocking leads against malaria parasite disease, which are in desperate need as resistance to frontline drugs increases. This project aims to identify small molecule inhibitors of Plasmaodium HKs as a novel modality to treat malaria. During this period, the collaborative team fully evaluated a top set of hits from the previously completed high-throughput hexokinase screen, and prioritized them for hit-to-lead development. A subset of these top compounds were also tested in advanced cell-based models and secondary assays to further characterize their activity. Several top hits were selected for activity validation and preliminary SAR assessments.